Regenerative Engineering Strategies in Cellular Senescence, Osteoarthritis and Cartilage Repair

Aging is marked by a gradual deterioration in the structural and functional integrity of organs and tissues, leading to an increased susceptibility to multiple joint diseases. Cartilage degeneration caused by aging is a prevalent factor contributing to osteoarthritis (OA) development, a condition that affects millions worldwide. The initiation of OA pathology is related to cellular senescence, which contributes to DNA damage, cell cycle repression, and the chronic level of inflammation. These senescent stem cells within knee joints are resistant to apoptosis, which display an altered secretion profile and diminished regenerative capacities. The development of interventions for OA aimed at delaying the aging process, alleviating the burden of age-related pathologies, and enhancing health span. Among emerging strategies, gene therapy has gained considerable attention as a transformative modality, utilizing advanced gene-editing and delivery technologies to modulate the molecular mechanisms underlying cellular aging and OA. However, specific deletion of p16 (a senescent marker) in chondrocytes did not inhibit the increased production of senescence-associated secretory phenotype factors during cartilage aging. Thus, identification of specific senescent subpopulations in cartilage aging and the development of new strategies focusing on rejuvenating or regenerating senescent chondrocytes are important for OA management.This Research Topic aims to identify and characterize the molecular pathways involved in cellular senescence and further use either advanced surgical or engineering methods to drive endogenous cartilage regeneration. Specifically, we further seek to develop pharmacological and gene-editing approaches that reverse senescence or rejuvenate it to enhance the regenerative potential of cartilage-resident cells. Additionally, the effectiveness of gene engineering of chondrocytes in promoting cartilage repair will be evaluated through both in vitro and in vivo studies. By advancing our knowledge in these areas, we aim to discover transformative therapies for OA.The scope of this Research Topic encompasses the study of senescent stem cells and the regenerative engineering approaches that could drive endogenous cartilage regeneration. To gather further insights into engineering senescent chondrocytes, we welcome articles addressing, but not limited to, the following themes:• Influence of the pericellular and extracellular matrix on cell senescence during OA progression.• Characterization and mechanistic studies of cartilage, infrapatellar fat pad, and synovial membrane-derived stem cell senescence.• Integration of organ-on-chip models to study senescent cellular interactions between different tissue types and the effects of cellular aging in pathological OA contexts.• Regenerative strategies utilizing juvenile cartilage-resident stem cells to support joint repair and regeneration.• Development of mechanical modulation approaches for studying mechanisms of senescent chondrocytes in OA.• Advanced surgical techniques, osteochondral transplantation, and osteotomies to promote cartilage health.• Exploration of other surgical, regenerative, and engineering strategies in cartilage aging and therapeutic responses to OA. Topic editors: Meng Feng, Ning Zhang, Qi Gao, Mengyao Sun, Zhuang Qian Source: https://www.frontiersin.org/research-topics/71950/regenerative-engineering-strategies-in-cellular-senescence-osteoarthritis-and-cartilage-repair